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31245056 Long-term safety of certolizumab pegol in rheumatoid arthritis, axial spondyloarthritis, p 2019 OBJECTIVE: To review long-term certolizumab pegol (CZP) safety across all approved indications: rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), psoriasis (PSO) and Crohn's disease (CD). METHODS: Data were pooled across 49 UCB-sponsored CZP clinical trials (27 RA, one axSpA, one PsA, five PSO, 15 CD) to August 2017. Serious adverse events (SAEs) of interest (infections, malignancies, autoimmunity/hypersensitivity events, major adverse cardiovascular events (MACE), gastrointestinal (GI) perforations, psoriasis events, laboratory abnormalities) and deaths were medically reviewed by an external expert committee, using predefined case rules. Incidence rates (IRs)/100 patient-years (PY) are presented by indication; standardised mortality and malignancy rates were calculated using WHO/GLOBOCAN/SEER databases. Pregnancies with maternal CZP exposure are also reported. RESULTS: Of 11 317 CZP-treated patients across indications (21 695 PY CZP exposure; maximum: 7.8 years), infections were the most common SAEs (overall IR: 3.62/100 PY; IRs ranged from 1.50/100 PY(PSO) to 5.97/100 PY(CD)). The IR for malignancies was 0.82/100 PY, including lymphoma (0.06/100 PY). MACE and GI perforation IRs in CZP-treated patients were 0.47/100 PY and 0.08/100 PY and were highest in RA and CD, respectively. Patients with PSO had the lowest SAE rates. The incidence of deaths and malignancies aligned with expected general population data. CONCLUSION: This extensive overview of the CZP safety profile in clinical trials, across all indications, provides large-scale confirmation of previous reports. No new safety signals or relevant non-disease-related laboratory abnormalities were identified. The study demonstrated some indication-specific differences in certain SAE rates that may be attributable to the underlying inflammatory disease.
30777365 Post-traumatic stress disorder and serum cytokine and chemokine concentrations in patients 2019 Oct OBJECTIVE: Although post-traumatic stress disorder (PTSD) is identified as a risk factor in the development of rheumatoid arthritis (RA), associations of PTSD with disease progression are less clear. To explore whether PTSD might influence disease-related measures of systemic inflammation in RA, we compared serum cytokine/chemokine (cytokine) concentrations in RA patients with and without PTSD. METHODS: Participants were U.S. Veterans with RA and were categorized as having PTSD, other forms of depression/anxiety, or neither based on administrative diagnostic codes. Multiplex cytokines were measured using banked serum. Associations of PTSD with cytokine parameters (including a weighted cytokine score) were assessed using multivariable regression, stratified by anti-CCP status and adjusted for age, sex, race, and smoking status. RESULTS: Among 1,460 RA subjects with mean (SD) age of 64 (11) years and disease duration of 11 (11) years, 91% were male, 77% anti-CCP positive, and 80% ever smokers. Of these, 11.6% had PTSD, 23.7% other depression/anxiety, and 64.7% had neither. PTSD, but not depression/anxiety, was associated with a higher cytokine score and number of high-concentration analytes in adjusted models, though this was limited to anti-CCP positive subjects. PTSD was associated with heightened expression of several individual cytokines including IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-17, IFN-γ, GM-CSF, MCP-1, and TNF-α. CONCLUSION: Anti-CCP positive RA patients with PTSD have higher serum cytokine concentrations than those without PTSD, demonstrating that systemic inflammation characteristic of RA is heightened in the context of this relatively common psychiatric comorbidity.
30468518 Comparison of rheumatoid arthritis (RA) and osteoarthritis (OA) based on microarray profil 2019 Jan The purpose of the present study was to investigate the underlying molecular mechanism of osteoarthritis (OA) and rheumatoid arthritis (RA) based on microarray profiles. Three human joint fibroblast-like synoviocytes (FLSs) microarray profiles including 26 OA samples, 33 RA samples, and 20 healthy control (HC) samples were downloaded from the GEO database. Differentially expressed genes (DEGs) between OA and HC (DEGsOA) and RA and HC (DEGsRA) were identified. Co-expressed and specific genes were analysed between DEGsOA and DEGsRA. Gene ontology, KEGG pathway enrichment, PPI network, and GSEA were performed to predict the function of DEGs. Two hundred seventy-six and 410 differential genes in DEGsOA and DEGsRA were observed. One hundred fifty coexpressed genes and 126 OA-specific genes (SELE, SERPINE1, and NFKBIA were the key genes) between DEGsOA and DEGsRA were enriched in the tumour necrosis factor (TNF) signalling pathway. However, 260 RA-specific genes of which the key genes were CCR5, CCR7, CXCR4, CCL5, and CCR4 were enriched in chemokine signalling pathway. Therefore, FLSs might exert an inflammatory effect by regulating TNF signalling pathway, targeting SELE, SERPINE1, and NFKBIA during the process of OA. Although TNF signalling pathway was also involved in the synovitis of RA, chemokine signalling pathway played the key role in RA FLSs mediating cell migration, invasion, and release of chemotaxis. In addition, CCR5, CCR7, CXCR4, CCL5, and CCR4 might be hub genes in RA. The different biomarkers and pathways identified in OA and RA may provide references for further study. SIGNIFICANCE OF THE STUDY: This study revealed the similar and different mechanisms of FLSs and different biomarkers that might with important regulatory effects on RA and OA. In OA, FLSs played an inflammatory role through TNF signalling pathway, targeting SELE, SERPINE1, and NFKBIA. Although TNF signalling pathway was also involved in the synovitis of RA, chemokine signalling pathway was a crucial pathway in mediating FLSs migration, invasion, and release of chemotaxis. CCR5, CCR7, CXCR4, CCL5, and CCR4 might be keys genes in RA. We expect that our results will bring more comprehensively understanding between RA and OA for researchers.
31819422 Co-Delivery of Prednisolone and Curcumin in Human Serum Albumin Nanoparticles for Effectiv 2019 BACKGROUND: Prednisolone (PD) is extremely effective for treating rheumatoid arthritis (RA). However, it distributes nonspecifically throughout the body and its use is associated with serious side effects, which promoted us to compound it into a phytomedicine for greater efficacy and safety. METHODS: We combined PD with curcumin (CU), an effective monomer from traditional Chinese medicine, and human serum albumin (HSA) in a nanoparticulate system (N-PD/CU) to compensate for the poor bioavailability of PD and CU. N-PD/CU was prepared by high-pressure homogenization, and its characteristics were evaluated in vitro. Next, we investigated its toxicity and mechanism of anti-inflammatory to macrophages. Finally, its pharmacokinetics, biodistribution and therapeutic efficacy were assessed in rats with adjuvant-induced arthritis (AIA). RESULTS: N-PD/CU showed a narrow size distribution around 150.4 ± 2.4 nm, a polydispersity index of 0.22 ± 0.02 and drug loading efficiency (DLE) of 88.75 ± 1.82% for PD and 85.79 ± 1.43% for CU. N-PD/CU showed sustained release of both drugs in vitro. N-PD/CU had no toxicity to macrophages in vitro on concentrations between 0.1 and 1.2 μmol/mL. In activated macrophages, N-PD decreased levels of pro-inflammatory cytokines, while N-CU increased levels of anti-inflammatory IL-10, and N-PD/CU exhibited best therapeutic effect in vitro, suggesting co-delivery of PD and CU may synergistically control the course of RA. In AIA rats, N-PD/CU accumulated in inflamed joints through the effect of extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration (ELVIS effect) in inflammatory lesion and showed higher therapeutic efficacy than single-loaded nanoparticles, either free drug on its own, or a simple mixture of the two drugs. CONCLUSION: This codelivery system based on HSA is a promising platform for combination chemotherapy in RA.
30374689 Common atherosclerosis genetic risk factors and subclinical atherosclerosis in rheumatoid 2019 Feb Rheumatoid arthritis (RA) is a common systemic autoimmune disease characterized by increased cardiovascular morbidity. Several previous studies assessed associations between common atherosclerotic genetic risk factors and subclinical atherosclerosis (SA) in RA patients, yet most of them gave negative results. We undertook a cross-sectional study to evaluate the association between previously reported SNPs and subclinical atherosclerosis in a cohort of Polish RA patients. 29 SNPs associated with atherosclerosis in general population were genotyped in 289 RA patients: 116 patients with SA (increased carotid intima-media thickness and/or presence of carotid plaque) and 173 patients without SA. To assess the cumulative effect of SNPs we calculated 3 weighted genetic risk scores: GRS(IMT), GRS(CP) and GRS(CAD), comprising intima-media thickness-associated SNPs, carotid plaque-associated SNPs and coronary artery disease-associated SNPs, respectively. None of the SNPs showed a significant association with SA. However, we found an association between SA and GRS(IMT). Interestingly, this association was limited to patients with short disease duration (P = 0.00004 vs. P > 0.5, for comparison of GRS(IMT) among patients within the 1st quartile of disease duration vs. others, respectively). Patients within the 1st quartile of disease duration were more frequently disease modifying anti-rheumatic drugs (DMARDs)-naïve and less frequently treated with biologics. Our study suggests that in patients with early RA subclinical atherosclerosis may be driven by similar genetic factors as in general population, while in long-lasting disease, the role common genetic risk factors may decrease. Possibly, this effect may be due to the influence of DMARDs.
31161316 [Special treatment in rheumatology-cross-sectoral quality-oriented selective contracts]. 2019 Jun In the last 4 years selective contracts according to §140a of the German Social Code Book V (SGB V) with three different health insurers were signed by the Professional Association of German Rheumatologists (BDRh) and from the beginning of the year 2018 by the management company of the association. The contracts were rolled out in five regions of Germany (Bavaria, Hesse, Mecklenburg-Western Pomerania, North Rhine and Saxony). Up to the end of 2018, 12,000 patients with chronic inflammatory rheumatic diseases were treated within the managed care of these contracts. The interface and the treatment pathways were initially consented with the associations of rheumatologists and general practitioners. The aim of the managed care was to provide the optimal quality in diagnostics and treatment and to improve management of rheumatic diseases. Quality indicators, such as treat-to-target principles, tight control, delegation to specially trained assistance personnel, patient education in rheumatoid arthritis (StruPi) and early arthritis consultation, are part of the managed care and are successfully promoted with incentive payments. Thus approximately 20% of the patients were enrolled for the first time in rheumatological care. The BDRh wants to promote the nationwide roll-out of this managed care in Germany with more participating health insurance funds.
31534975 TNFAIP3 Gene Polymorphisms in Three Common Autoimmune Diseases: Systemic Lupus Erythematos 2019 Autoimmune diseases (AIDs) are complex diseases characterized by persistent or recurrent inflammation, alteration of immune response, and production of specific autoantibodies. It is known that different AIDs share several susceptibility genetic loci. Tumor necrosis factor alpha inducible protein 3 (TNFAIP3) encodes the ubiquitin-modifying enzyme A20, which downregulates inflammation by restricting NF-κB, a transcription factor that regulates expression of various proinflammatory genes. Variants in TNFAIP3 gene have been described as associated with susceptibility to several AIDs. Here, we analyzed two TNFAIP3 polymorphisms in Italian patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjogren's syndrome (pSS), to verify if the genetic variability of TNFAIP3 gene is involved in genetic predisposition to AIDs also in the Italian population. We recruited 313 SLE patients, 256 RA patients, 195 pSS patients, and 236 healthy controls. Genotyping of rs2230926 and rs6920220 in TNFAIP3 gene was performed by an allelic discrimination assay. We carried out a case/control association study and a genotype/phenotype correlation analysis. A higher risk to develop SLE was observed for rs2230926 (P = 0.02, OR = 1.92). No association was observed between this SNP and the susceptibility to pSS or RA. However, the rs2230926 variant allele seems to confer a higher risk to develop lymphoma in pSS patients, while in RA patients, the presence of RF resulted significantly associated with the variant allele. Regarding the rs6920220 SNP, we observed a significant association of the variant allele with SLE (P = 0.03, OR = 1.53), pSS (P = 0.016, OR = 1.69), and RA (P = 0.0001, OR = 2.35) susceptibility. Furthermore, SLE patients carrying the variant allele showed a higher risk to develop pericarditis, pleurisy, and kidney complications. Our results support the importance of the TNFAIP3 gene variant role in the development of different autoimmune diseases in the Italian population and furtherly confirm a sharing of genetic predisposing factors among these three pathologies.
31638264 IL‑1β increases the expression of inflammatory factors in synovial fluid‑derived fibr 2019 Dec Interleukin (IL)‑1β serves a crucial role in the progression of rheumatoid arthritis. Previous studies have indicated that the ERK/STAT1 signaling pathway may be involved in the inflammatory response in synovial fluid‑derived fibroblast‑like synoviocytes (sfd‑FLSs). However, the molecular mechanisms underlying the pathological effects of the inflammatory factors induced by IL‑1β in sfd‑FLSs remain unclear. The aim of the present study was to investigate the IL‑1β‑mediated signaling pathways involved in the expression of inflammatory factors in sfd‑FLSs and in a rat model of rheumatoid arthritis. Reverse transcription‑quantitative PCR, western blotting, and immunohistochemistry were used to analyze the role of IL‑1β in the rat model of rheumatoid arthritis. The results suggested that IL‑1β administration exacerbated rheumatoid arthritis, bone injury and increased the expression levels of inflammatory factors, such as IL‑17 and tumor necrosis factor α (TNF‑α), whereas treatment with anti‑IL‑1β exhibited opposite effects. In vitro experiments in sfd‑FLSs further suggested that treatment with IL‑1β influenced the expression levels of various inflammatory factors. In specific, IL‑1β increased the expression of IL‑17 and TNF‑α, and decreased the expression of IL‑6 and IL‑10 in sfd‑FLSs. Additionally, treatment with IL‑1β increased the mRNA expression and protein phosphorylation of NF‑κB, ERK and STAT1 in sfd‑FLSs. Treatment with anti‑IL‑1β exhibited opposite effects on the expression levels of inflammatory factors and suppressed the NF‑κB‑mediated ERK‑STAT1 signaling pathway activation in sfd‑FLSs. Finally, treatment with a NF‑κB inhibitor suppressed the effects of IL‑1β, and NF‑κB overexpression reversed the effects of anti‑IL‑1β on the expression levels of IL‑17, TNF‑α, NF‑κB, ERK and STAT1. In conclusion, the present results demonstrated that treatment with IL‑1β increased the expression levels of inflammatory factors in sfd‑FLSs via the regulation of the NF‑κB‑mediated ERK/STAT1 signaling pathway in a rat model of rheumatoid arthritis. Therefore, the NF‑κB/ERK/STAT1 signaling pathway may represent a potential target for the development of novel treatments for rheumatoid arthritis.
30728072 Rheumatoid arthritis reprograms circadian output pathways. 2019 Feb 6 OBJECTIVE: We applied systems biology approaches to investigate circadian rhythmicity in rheumatoid arthritis (RA). METHODS: We recruited adults (age 16-80 years old) with a clinical diagnosis of RA (active disease [DAS28 > 3.2]). Sleep profiles were determined before inpatient measurements of saliva, serum, and peripheral blood mononuclear leukocytes (PBML). Transcriptome and proteome analyses were carried out by RNA-SEQ and LC-MS/MS. Serum samples were analysed by targeted lipidomics, along with serum from mouse collagen induced-arthritis (CIA). Bioinformatic analysis identified RA-specific gene networks and rhythmic processes differing between healthy and RA. RESULTS: RA caused greater time-of-day variation in PBML gene expression, and ex vivo stimulation identified a time-of-day-specific RA transcriptome. We found increased phospho-STAT3 in RA patients, and some targets, including phospho-ATF2, acquired time-of-day variation in RA. Serum ceramides also gained circadian rhythmicity in RA, which was also seen in mouse experimental arthritis, resulting from gain in circadian rhythmicity of hepatic ceramide synthases. CONCLUSION: RA drives a gain in circadian rhythmicity, both in immune cells, and systemically. The coupling of distant timing information to ceramide synthesis and joint inflammation points to a systemic re-wiring of the circadian repertoire. Circadian reprogramming in response to chronic inflammation has implications for inflammatory co-morbidities and time-of-day therapeutics.
31502378 Immunomodulatory effect of human bone marrow-derived mesenchymal stromal/stem cells on per 2020 Jan Rheumatoid arthritis (RA) is a Th1/Th17-mediated autoimmune disease whose current treatment, consisting in the blockage of inflammatory cytokines by disease-modifying antirheumatic drugs, is not effective for all patients. The therapeutic potential of mesenchymal stromal/stem cells' (MSCs) immunomodulatory properties is being explored in RA. Here, we investigate the effect of human bone marrow (BM)-MSCs on the expression of cytokines involved in RA physiopathology by the distinct functional compartments of CD4(+) and CD8(+) T cells from RA patients. Peripheral blood mononuclear cells from healthy individuals (n = 6) and RA patients (n = 12) were stimulated with phorbol myristate acetate plus ionomycin and cultured in the presence/absence of BM-MSCs. The expression of (interleukin) IL-2, tumor necrosis factor alpha (TNF-α), and interferon-gamma (IFN-γ) was evaluated in naive, central memory, effector memory, and effector CD4(+) and CD8(+) T cells, whereas IL-6, IL-9, and IL-17 expression was measured in total CD4(+) and CD8(+) T cells. mRNA expression of IL-4, IL-10, transforming growth factor beta (TGF-β), cytotoxic T-lymphocyte-associated antigen 4, and/or forkhead box P3 was quantified in fluorescence-activated cell sorting-purified CD4(+) T cells, CD8(+) T cells, and CD4(+) Treg. BM-MSCs inhibited the production of TNF-α, IL-17, IL-6, IL-2, IFN-γ, and IL-9 by T cells from RA patients, mainly by reducing the percentage of cells producing cytokines. This inhibitory effect was transversal to all T cell subsets analyzed. At mRNA level, BM-MSCs increased expression of IL-10 and TGF-β by CD4(+) and CD8(+) T cells. BM-MSCs displayed a striking inhibitory action over T cells from RA patients, reducing the expression of cytokines involved in RA physiopathology. Remarkably, BM-MSC-derived immunomodulation affected either naive, effector, and memory T cells.
31131959 A diagnosis of rheumatoid arthritis, endometriosis or IBD is associated with later onset o 2019 Sep BACKGROUND: Widespread pain is a common comorbidity in several chronic diseases and is suspected to be caused by pain resulting from the underlying disease that has provoked a state of central sensitization. However, this argument is currently limited by evidence that has insufficiently captured the temporal nature of the relationship between diagnosis of the underlying disease and onset of widespread pain. The aim of this study was to investigate if patients with rheumatoid arthritis (RA), endometriosis or inflammatory bowel disease (IBD), have a higher risk of developing widespread pain (fibromyalgia or chronic widespread pain [CWP]). METHODS: Using the Swedish Skåne Healthcare register on health care consultation, a cohort of 889,938 adult patients were followed from 2007 to 2016 and incident cases of RA, endometriosis or IBD and of fibromyalgia and CWP were identified by registered diagnoses. Using Poisson regression, we calculated incidence rate ratios (IRR) adjusted for sex, age, education and propensity to seek health care. RESULTS: For patients with RA the IRR for later fibromyalgia was 3.64 (95% CI: 2.75-4.81) compared to patients without RA, for CWP it was 2.96 (95% CI: 1.81-4.86). For endometriosis patients the IRR for fibromyalgia was 2.83 (95% CI: 1.96-4.08) and for CWP 5.02 (95% CI: 3.10-8.13). IBD patients had an IRR = 2.32 (95% CI: 1.58-3.42) for fibromyalgia and 1.42 (95% CI: 0.93-2.17) for CWP. CONCLUSIONS: This study shows that RA, endometriosis and IBD are all risk factors for later fibromyalgia and CWP, consistent with a hypothesis of central sensitization as an effect of a painful underlying condition. SIGNIFICANCE: We show that RA, endometriosis and IBD predisposes for later fibromyalgia and CWP, a common hypothesis previously difficult to verify due to lack of longitudinal data. The results inform further research regarding the aetiology of fibromyalgia and CWP and stress the need of clinical focus on the pain itself in chronic diseases with pain as a symptom.
31530401 The association between gravidity, parity and the risk of developing rheumatoid arthritis: 2020 Apr OBJECTIVE: To establish if gravidity and parity associate with the development of rheumatoid arthritis (RA), and to establish if this effect is influenced by the time elapsed since pregnancy/childbirth, the number of pregnancies/childbirths, and serological status, through systematically reviewing the literature and undertaking a meta-analysis. METHODS: We searched Medline/EMBASE (from 1946 to 2018) using the terms "rheumatoid arthritis.mp" or "arthritis, rheumatoid/" and "pregnancy.mp" or "pregnancy/" or "parity.mp" or "parity/" or "gravidity.mp" or "gravidity/" (observational study filter applied). Case-control/cohort studies that examined the relationship between parity/gravidity and the risk of RA in women were included. Studies reporting effect size data for RA in ever vs. never parous/gravid women as ORs/RRs with 95% confidence intervals were included in a meta-analysis. Other relationships (i.e. risk by pregnancy/childbirth numbers) were analysed descriptively. RESULTS: Twenty studies (from 626 articles) met our inclusion criteria, comprising 14 case-control (4799 cases; 11,941 controls) and 6 cohort studies (8575 cases; 2,368,439 individuals). No significant association was observed in the meta-analysis of studies reporting the risk of RA in ever vs. never parous women (OR 0.91; 95% CI 0.80-1.04) and ever vs. never gravid women (OR 0.86; 95% CI 0.46-1.62). No consistent evidence of a relationship between the number of pregnancies/childbirths and RA risk was seen. No significant association was observed between being pregnant, or in the immediate post-partum period, and the risk of developing RA. CONCLUSION: Our systematic review does not support the concept that gravidity and parity are associated with the risk of RA development.
30732168 Assessment of nutritional status by dual X-Ray absorptiometry in women with rheumatoid art 2019 Feb Rheumatoid arthritis (RA) has been related to an impairment of the nutritional status. Body mass index (BMI) has been used but questions arise about how to properly evaluate nutritional status in RA patients. Few studies have evaluated it by dual-energy X-ray absorptiometry.In women with RA, to analyze:Case-control study including 89 women with RA. The control group was composed by 100 patients affected by non-inflammatory rheumatic disorders. Study variables included age, RA duration, history, activity and disability, and in relation to nutritional status: BMI, serum albumin (ALB), whole body DXA assessment, and skeletal muscle index (SMI).Mean age of patients was 62 ± 8 years, mean duration of RA was 14 ± 9 years, mean disease activity score (DAS28) was 3.7 ± 1.4 and mean Health Assessment Questionnaire was 0.88 ± 0.77. BMI was 27.43 ± 5.16 Kg/m in patients and 27.78 ± 3.98 Kg/m in controls (P: ns). ALB was within normal range in all patients.By whole body DXA, RA patients presented a statistically significant lower lean mass in all locations and lower fat mass in limbs than controls. Patients had a redistribution of fat mass to trunk. Lean mass directly correlated with fat mass.Neither BMI nor ALB correlated with DXA parameters.BMI, appendicular lean mass and SMI correlated inversely with disease duration. Trunk lean mass correlated inversely, and fat mass directly, with RA disability parameters.RA patients fulfilled criteria of sarcopenia in 44% of cases versus 19% of controls (P <.001). In RA patients, regarding SMI, BMI showed a high specificity to detect sarcopenia (94% of the patients with low BMI had sarcopenia) but low sensitivity (47% of the patients with normal BMI or overweight had sarcopenia).RA patients have an impairment of nutritional status associated to disease duration that looks like sarcopenia and that is not predicted by BMI.
30407878 GDF11 antagonizes TNF-α-induced inflammation and protects against the development of infl 2019 Mar Growth differentiation factor 11 (GDF11), a key member of the TGF-β superfamily, plays critical roles in various medical conditions. Recently, GDF11 was found to suppress the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway and protect against inflammation. This study aimed to investigate the role of GDF11 in the development of rheumatoid arthritis (RA). We demonstrated that GDF11 treatment antagonized TNF-α-induced inflammation in macrophages. Moreover, GDF11 inhibited the development of arthritis in the collagen-induced arthritis and collagen antibody-induced arthritis models. Local gene transfer of GDF11 via adeno-associated virus exerted therapeutic effects, while local knockdown of GDF11 exaggerated inflammation in our collagen-induced arthritis model, as detected by expression levels of inflammatory biomarkers and the destruction of joint structures. Additionally, the results from both in vitro experiments and luciferase reporter gene mouse experiments implied that the NF-κB pathway might play a critical role in the therapeutic effect of GDF11 in RA. This study presents GDF11 as a potential target for the treatment of inflammatory arthritis, including RA.-Li, W., Wang, W., Liu, L., Qu, R., Chen, X., Qiu, C., Li, J., Hayball, J., Liu, L., Chen, J., Wang, X., Pan, X., Zhao, Y. GDF11 antagonizes TNF-α-induced inflammation and protects against the development of inflammatory arthritis in mice.
30809303 Enhanced Therapeutic Effect of RGD-Modified Polymeric Micelles Loaded With Low-Dose Methot 2019 Angiogenesis plays an essential role in the progression of rheumatoid arthritis (RA). RGD peptide shows high affinity and selectivity for integrin α(v)β(3,) which is one of the most extensively examined target of angiogenesis. Nimesulide could improve the anti-rheumatic profile of methotrexate. But the clinical application was limited due to water-insolubility of both methotrexate and nimesulide and lacking targeting ability. Therefore, this study aimed to design a targeted drug delivery system of micelles mediated by RGD plus the passive targeting of micelles to solve the application problems of methotrexate and nimesulide (M/N), and thus enhance their combined therapeutic effect on RA. Methods: RGD was conjugated with NHS-PEG-PLA to form RGD-PEG-PLA for the preparation of RGD-modified drug-loaded micelles (R-M/N-PMs). The size and zeta potential of micelles were measured by dynamic light scattering. Morphology was detected by transmission electron microscopy. The inhibition effect of R-M/N-PMs on angiogenesis was assessed by the chick chorioallantoic membrane assay. The real-time fluorescence imaging analysis was conducted to examine the in vivo distribution of the fluorescence-labeled R-M/N-PMs. Rats arthritis model induced by Freund's adjuvant was used to evaluate the in vivo anti-inflammatory efficacy of R-M/N-PMs. Results: The in vitro study indicated successful development of R-M/N-PMs. R-M/N-PMs could markedly suppress the angiogenesis of chick embryos. The fluorescence-labeled R-M/N-PMs mainly accumulated in arthritic joints. RGD enhanced the targeting ability of micelles and thus promoted retention of micelles in arthritic joints. Moreover, R-M/N-PMs significantly alleviated the joint swelling while reducing bone erosion and serum levels of inflammatory cytokines. It helped to recover the bone microstructure of arthritic rats. Conclusion: Our results confirmed that the targeted delivery of the combination of a low dose of methotrexate and nimesulide mediated by RGD-modified polymeric micelles could enhance the therapeutic effect on rheumatoid arthritis. These findings provide a promising potential for the clinical therapy of rheumatoid arthritis.
30927217 Lay Perspectives of Quality of Life in Rheumatoid Arthritis Patients: The Relevance of Aut 2019 Nov The aim of this study is to increase the understanding of Quality of Life (QoL) in rheumatoid arthritis (RA) patients and explore the personal features of living with the disease. Sixty-two RA patients (M(Age) = 56.7; SD = 11.2; female = 83.9%) were interviewed. Assessment included topics on medical condition, functional status (HAQ-DI), and on their perceived difficulties and worries in having RA. Patients' overall definition of QoL was also inquired. Most patients lived with RA for a long period of time (M = 16.5 years; SD = 11.6) and presented moderate HAQ-DI scores (M = 1.37; SD = 0.75). Main features of QoL in RA highlight the importance given to physical health, particularly to independence and autonomy. Psychological distress emerged also as an important feature of living with RA, constraining a good QoL. Medical staff should consider the RA patients' emotional needs, expectations, and main perceived determinants of their QoL to better help them.
31802210 The effects of exercise on cardiovascular disease risk factors and cardiovascular physiolo 2020 Mar Cardiovascular disease (CVD) morbidity and mortality is highly prevalent in patients with rheumatoid arthritis (RA) with debilitating effects for the individual as well as significant healthcare impact. Current evidence demonstrates that engaging in aerobic and resistance exercise (i.e. structured physical activity) can significantly improve patient-reported and clinical index-assessed outcomes in RA. In addition to this, engagement in exercise programmes improves, in a dose-dependent manner, the risk of developing CVD as well as CVD symptoms and outcomes. The present narrative review uses evidence from systematic reviews and meta-analyses as well as controlled trials, to synthesize the current state-of-the-art on the potential effects of aerobic and resistance exercise on CVD risk factors as well as on cardiac and vascular function and structure in people with RA. Where there is a lack of evidence in RA to explain potential mechanisms, relevant studies from the general population are also discussed and linked to RA.
30816022 Adult outcome of juvenile idiopathic arthritis: A nationwide population-based retrospectiv 2019 Jul OBJECTIVE: To clarify the development of juvenile idiopathic arthritis (JIA) to adult-onset autoimmune diseases in a population-based study in Taiwan. METHODS: We analyzed data of 107 433 children born between 1990 and 1997 from the National Taiwan Health Insurance Database. There were 262 JIA patients and 107 171 individuals without JIA who were selected and followed up until December 2013 to investigate their outcomes of adult-onset autoimmune diseases after reaching 16 years of age. The adjusted hazard ratios (aHRs) including 95% confidence intervals (95% CI) of adult-onset autoimmune diseases were calculated using the Cox proportional regression model among different age groups. RESULTS: The incidence rate for patients with a history of JIA was 83.56 per 10(5) person-months for rheumatoid arthritis (RA), 16.61 for systemic lupus erythematosus (SLE), 58.39 for ankylosing spondylitis (AS), and 33.26 for psoriatic diseases. The aHRs were 29.60 for any autoimmune disease, 129.52 for RA, 10.01 for SLE, 49.62 for AS, and 8.20 for psoriatic diseases. Compared with non-JIA individuals, the aHRs of adult-onset autoimmune diseases were 34.87 (95% CI: 4.85-250.62) at the onset age of 3-5 years, 12.01 (95% CI: 2.99-48.26) at the age of 6-10 years, and 45.80 (95% CI: 29.69-70.64) at the age of 11-15 years. CONCLUSION: Children with JIA were at an increased risk of developing RA, AS, psoriatic disease, and SLE in adulthood.
31127317 Increased risk of osteoporotic vertebral fracture in rheumatoid arthritis patients with ne 2019 Aug INTRODUCTION: Both cardiovascular diseases (CVD) and osteoporosis are common comorbidities in rheumatoid arthritis (RA) patients. Although accumulating evidence indicates a link between CVD and osteoporotic fracture, whether CVD contributes to osteoporotic fracture risk in RA has yet to be explored. We examined the incidence rate and risk factors of osteoporotic vertebral fracture in RA patients with new-onset CVD (RA-CVD) and evaluated the effects of medications on such fracture risk. METHODS: A retrospective study was conducted using a nationwide database from 2000 to 2010: 1267 RA-CVD and 1267 non-CVD patients were enrolled from 30,507 patients with newly diagnosed RA. The main outcome was the development of osteoporotic vertebral fracture. After being adjusted for age, gender, and comorbidities, the Cox proportional hazard model was used to identify independent factors contributing to osteoporotic vertebral fracture. RESULTS: The adjusted hazard ratio (aHR) of developing osteoporotic vertebral fracture was 1.47-fold greater in RA-CVD group than in non-CVD group (95% confidence interval 1.19-1.81, p < 0.001). Both the age above 40 years and female gender were significant risk factors for developing osteoporotic vertebral fracture in RA-CVD patients. Using patients not taking medication as a reference group, the aHR of osteoporotic vertebral fracture was significantly lower in those receiving statins (0.50), low-dose corticosteroids (0.57), or hydroxychloroquine (0.12). CONCLUSIONS: The risk of osteoporotic vertebral fracture was significantly increased in RA-CVD patients, particularly women above 40 years of age, and could be reduced by statin therapy. However, the protective effect of low-dose corticosteroids or hydroxychloroquine on osteoporotic vertebral fracture risk needs further validation.
31311230 Rheumatoid Arthritis Complicated by Myositis and Vasculitic Neuropathy: A Rare Association 2019 Apr Rheumatoid arthritis (RA) is a multisystem disease with a variety of manifestations. Vasculitis and myositis are two very rare complications of RA. However, the coexistence of both of these complications in the same patient is extremely rare in medical literature. We here present such a rare association of clinical features in a 36 year old male patient with RA. He had RA for around four years before development of these complications almost simultaneously. The patient was treated with rituximab and oral steroids. The myositis component responded promptly but the vasculitic neuropathy was very slow to respond.